{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:27:15Z","timestamp":1786602435392,"version":"build-2736575974"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a major cause of cancer\u2010related mortality, and effective prognostic stratification remains urgently needed. Ribonucleotide reductase (RR), consisting mainly of RRM1 and RRM2, plays a critical role in nucleotide metabolism and tumor progression. This study aimed to develop an RR\u2010related long non\u2010coding RNA (lncRNA) signature for predicting prognosis and exploring potential therapeutic implications in HCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic and clinical data from 377 HCC patients in The Cancer Genome Atlas (TCGA) database were analyzed. Molecular subgroups were identified based on RRM1 and RRM2 expression. Differentially expressed RR\u2010related lncRNAs were screened, and an RR\u2010indexed lncRNA prognostic signature (RILPS) was established using univariate Cox and LASSO Cox regression analyses. A nomogram integrating RILPS and M stage was constructed, followed by analyses of immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), pathway enrichment, and drug sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two distinct RRM1\/RRM2\u2010associated molecular clusters were identified. A 65\u2010lncRNA\u2010based RILPS model was developed and effectively stratified HCC patients into different prognostic groups. The RILPS\u2010M stage nomogram showed favorable predictive performance, with AUC values of 0.767, 0.800, and 0.820 for 1\u2010, 3\u2010, and 5\u2010year overall survival, respectively. The high\u2010RILPS group exhibited increased immune infiltration, higher TMB, and MSI characteristics, whereas the low\u2010RILPS group was enriched in metabolic pathways. Key lncRNAs, including NBAT1, LINC01138, and LINC00671, were associated with HCC prognosis and may contribute to tumor progression. Drug sensitivity analysis suggested potential therapeutic differences between RILPS\u2010defined subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The RR\u2010related lncRNA signature integrates prognostic, immune, and metabolic features in HCC. RILPS may serve as a promising tool for risk stratification and personalized treatment guidance, while the identified lncRNAs provide potential candidates for further mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1908145","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:33:20Z","timestamp":1786599200000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A prognostic lncRNA signature associated with ribonucleotide reductase predicts overall survival and immune landscape in hepatocellular carcinoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Kepu","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Surgery, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, 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